Failure of macrophage activation to induce pulmonary fibrosis in asbestos-exposed guinea-pigs

Our plain-English summary of Failure of macrophage activation to induce pulmonary fibrosis in asbestos-exposed guinea-pigs, by R.J. Emerson, P.J. Cole (British Journal of Experimental Pathology, 1983).

The study

• Authors: R.J. Emerson, P.J. Cole
• Journal: British Journal of Experimental Pathology
• Published: 1983;64(1):66-74
• Read it: PubMed · Free full text

Abstract

Inhalation of asbestos by specific-pathogen-free (SPF) guinea-pigs the macrophages of which were systemically activated with Freund's complete adjuvant and/or M. tuberculosis (Strain H37Ra) induced a diffuse pulmonary mononuclear-cell infiltration of the interstitium and air space. The severity of the reactions to the various insults was dependent on the treatment given. Although there was no histological evidence of increased collagen, there was a diffuse increase in reticulin in animals which were exposed to asbestos and the macrophages of which were activated. However, even in the case where severe pulmonary inflammatory changes occurred complete resolution of the response took place within 1 year. Therefore in this model activation of macrophages does not have a detrimental effect after inhalation of asbestos.

In plain English

In this experiment in specific-pathogen-free female guinea-pigs, the authors tested whether activated macrophages (lung scavenger cells) would make inhaled asbestos cause lung scarring (fibrosis). Activation used injections of Freund's complete adjuvant and/or M. tuberculosis (strain H37Ra). Animals inhaled UICC Rhodesian chrysotile A asbestos at 5,000 fibres/cc air for 8 hours on 2 consecutive days. They then stayed in the chamber overnight, raising more, unmeasured dust. All treated groups developed mononuclear-cell lung inflammation, and most of their macrophages looked activated; those of the controls did not. Treated groups differed from untreated controls, but from one another only in degree. Lesions in animals given asbestos plus both agents were more extensive, appeared earlier and resolved more slowly. Asbestos bodies appeared by 4 weeks and persisted all year. Thickened reticulin fibres appeared, but no collagen increase was seen. At 9 and 12 months the inflammation was resolving: lesions shrank, reticulin was resorbed, and lungs eventually looked normal. The authors concluded that macrophage activation did not enhance fibrosis after short asbestos inhalation. They cautioned that the dose may have been too small and dose-response studies were needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (inhalation study with lung histology and electron microscopy)
• Who was studied: Female specific-pathogen-free Dunkin-Hartley guinea-pigs weighing 300-350 g, divided into 8 groups of 3 animals each, including an untreated control group (Group N). The work was done at the Cardiothoracic Institute, Brompton Hospital, London. Study dates are not given.
• Exposure: UICC Rhodesian chrysotile A asbestos, monitored at 5,000 fibres/cc air for 8 h on 2 consecutive days while the dust generator ran. Animals also stayed in the chamber overnight, when their movements raised more dust; that concentration was not measured. Macrophages were activated with Freund's complete adjuvant (footpad injection) and/or M. tuberculosis strain H37Ra (injection under the skin), alone or in combination with asbestos.
• Main results:
  • Numerous mononuclear cells were present in the alveolar spaces of all treated groups.
  • In treated groups, most macrophages showed features suggesting an activated state.
  • In untreated controls, alveolar macrophages were hard to find. When present, they appeared mature and lacked features of activation.
  • All treated groups differed from the untreated controls during the inflammatory process.
  • The experimental groups could not be distinguished from one another by light microscopy. Their changes differed only quantitatively.
  • In the group given asbestos, Freund's complete adjuvant and H37Ra (Group AFM), lesions were more extensive, appeared earlier and were slower to resolve than in other treated groups.
  • Combined treatment with any 2 agents generally accentuated the inflammatory response compared with a single treatment.
  • Asbestos bodies were seen from 4 weeks and persisted for the whole year of the study. Mycobacteria, amyloid deposits and increases in collagen were not observed.
  • During the inflammatory phase, thickened reticulin fibres appeared in the interstitial spaces, and finer new fibres formed within alveoli.
  • Animals killed at 9 and 12 months after any treatment showed resolution of the inflammatory response.
  • Lesions gradually became smaller, reticulin was resorbed, and the lung tissue eventually became normal in appearance.
• The authors' conclusion: The authors concluded that systemic macrophage activation does not enhance the establishment of pulmonary fibrosis in guinea-pigs that inhaled asbestos for a short time.
• Limitations the authors state:
  • The amount of asbestos able to interact with activated cells may have been too small to cause fibrosis, however the cells were activated.
  • Dose-response studies in a similar model would be needed to answer this question.
  • The fibre concentration in the chamber was not measured while the animals stayed in it overnight, when their own movement raised further dust.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Pulmonary Fibrosis, Collagen.

Related studies

• Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure — S. Murthy, J.L. Larson-Casey, et al. (2015)
• Biochemical changes and pulmonary response of guinea pigs to asbestos dust — J. Singh, M.U. Beg, et al. (1976)
• Lung cell reactions in guinea pigs after inhalation of asbestos (amosite) — M. Sjöstrand, R. Rylander, et al. (1989)
• Cytotoxic effect of asbestos on macrophages in different activation states — A. Wright, K. Donaldson, et al. (1983)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)

Browse more research in British Journal of Experimental Pathology, or return to medical research.